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Influenza polymerase

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https://www.readbyqxmd.com/read/28214222/necessity-to-critically-review-the-automatic-results-of-the-xpert-flu-assay
#1
Ilka Engelmann, Enagnon Kazali Alidjinou, Mouna Lazrek, Anny Dewilde, Didier Hober
While using the Xpert Flu assay we became aware of false-negative results. The study aimed to analyze the causes of these false-negative results. One hundred fifty-nine respiratory specimens were tested in the Xpert Flu assay and in multiplex reverse transcription-polymerase chain reactions (RT-PCRs) for respiratory viruses. Discordant specimens were tested in the Influenza A/B r-gene assay. One hundred fifty-two (96%) and 151 (95%) specimens yielded concordant results for influenza A and B, respectively. Fifteen specimens tested negative in the Xpert Flu assay and positive in a multiplex RT-PCR...
February 2, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28208721/evolution-and-divergence-of-h3n8-equine-influenza-viruses-circulating-in-the-united-kingdom-from-2013-to-2015
#2
Adam Rash, Rachel Morton, Alana Woodward, Olivia Maes, John McCauley, Neil Bryant, Debra Elton
Equine influenza viruses (EIV) are a major cause of acute respiratory disease in horses worldwide and occasionally also affect vaccinated animals. Like other influenza A viruses, they undergo antigenic drift, highlighting the importance of both surveillance and virus characterisation in order for vaccine strains to be kept up to date. The aim of the work reported here was to monitor the genetic and antigenic changes occurring in EIV circulating in the UK from 2013 to 2015 and to identify any evidence of vaccine breakdown in the field...
February 8, 2017: Pathogens
https://www.readbyqxmd.com/read/28207989/predictors-of-influenza-a-molecular-viral-shedding-in-hutterites-communities
#3
Biao Wang, Margaret L Russell, Kevin Fonseca, David J D Earn, Gregory Horsman, Paul Van Caeseele, Khami Chokani, Mark Vooght, Lorne Babiuk, Stephen D Walter, Mark Loeb
BACKGROUND: Patterns of influenza molecular viral shedding following influenza infection have been well established; predictors of viral shedding however remain uncertain. OBJECTIVES: We sought to determine factors associated with peak molecular viral load, duration of shedding, and viral area under curve (AUC) in children and adult Hutterite colony members with laboratory confirmed influenza. METHODS: A cohort study was conducted in Hutterite colonies in Alberta, Canada...
February 16, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28202040/subcellular-localization-and-interactions-of-infectious-salmon-anemia-virus-isav-m1-and-nep-as-well-as-host-hsc70
#4
Wenting Zhang, Chengzhi Cai, Li Lin, Yizhi Jane Tao, Meilin Jin
BACKGROUND: Infectious salmon anemia virus (ISAV) is an important fish pathogen that causes high mortality in farmed Atlantic salmon. The ISAV genome consists of eight single-stranded, negative-sense RNA segments. The six largest segments contain one open reading frame (ORF) each, and encode three polymerase proteins, nucleoprotein, fusion protein, and hemagglutinin esterase protein. The two smallest segments contain more than one ORF each. The segment 7 encodes non-structural protein 1 (NS1) and nuclear export protein (NEP), while segment 8 encodes matrix protein 1 and 2 (M1 and M2)...
February 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28197322/discovery-of-novel-orally-bioavailable-%C3%AE-amino-acid-azaindole-inhibitors-of-influenza-pb2
#5
Luc J Farmer, Michael P Clark, Michael J Boyd, Emanuele Perola, Steven M Jones, Alice Tsai, Marc D Jacobs, Upul K Bandarage, Mark W Ledeboer, Tiansheng Wang, Hongbo Deng, Brian Ledford, Wenxin Gu, John P Duffy, Randy S Bethiel, Dean Shannon, Randal A Byrn, Joshua R Leeman, Rene Rijnbrand, Hamilton B Bennett, Colleen O'Brien, Christine Memmott, Kwame Nti-Addae, Youssef L Bennani, Paul S Charifson
In our efforts to develop novel small-molecule inhibitors for the treatment of influenza, we utilized molecular modeling and the X-ray crystal structure of the PB2 subunit of the influenza polymerase to optimize a series of acyclic β-amino acid inhibitors, highlighted by compound 4. Compound 4 showed good oral exposure in both rat and mouse. More importantly, it showed strong potency versus multiple influenza-A strains, including pandemic 2009 H1N1 and avian H5N1 strains and showed a strong efficacy profile in a mouse influenza model even when treatment was initiated 48 h after infection...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28193653/the-pa-endonuclease-inhibitor-ro-7-protects-mice-from-lethal-challenge-with-influenza-a-or-b-viruses
#6
Jeremy C Jones, Bindumadhav M Marathe, Peter Vogel, Rodolfo Gasser, Isabel Najera, Elena A Govorkova
Current influenza treatment relies on a single class of antiviral drugs, the neuraminidase inhibitors (NAIs), raising concern over the potential emergence of resistant variants and necessitating the development of novel drugs. In recent years, investigational inhibitors targeting the endonuclease activity of the influenza acidic polymerase (PA) protein have yielded encouraging results, although there are only limited data on their in vivo efficacy. Here, we examined the antiviral potential of the PA endonuclease inhibitor RO-7 in prophylactic and therapeutic regimens in BALB/c mice inoculated with influenza A/California/04/2009 (H1N1)pdm09 or B/Brisbane/60/2008 viruses, which represent currently circulating antigenic variants...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28182741/etiology-of-severe-pneumonia-in-ecuadorian-children
#7
Sivani Jonnalagadda, Oswaldo Rodríguez, Bertha Estrella, Lora L Sabin, Fernando Sempértegui, Davidson H Hamer
BACKGROUND: In Latin America, community-acquired pneumonia remains a major cause of morbidity and mortality among children. Few studies have examined the etiology of pneumonia in Ecuador. METHODS: This observational study was part of a randomized, double blind, placebo-controlled clinical trial conducted among children aged 2-59 months with severe pneumonia in Quito, Ecuador. Nasopharyngeal and blood samples were tested for bacterial and viral etiology by polymerase chain reaction...
2017: PloS One
https://www.readbyqxmd.com/read/28176519/-favipiravir-a-new-concept-of-antiviral-drug-against-influenza-viruses
#8
REVIEW
J Reina, N Reina
Favipiravir (T-705) is a new antiviral drug with strong inhibitory activity on RNA-dependent RNA polymerase of most RNA virus genome. All the influenza viruses have been shown fully sensitive to this new antiviral, including genetic strains to neuraminidase inhibitors (oseltamivir) resistance. Its mechanism of action lies in blocking viral replication and induction of lethal mutagenesis which determines the loss of infective activity of influenza viruses. Its activity is particularly intense in the respiratory tract, decreasing the viral load to non-infectious levels...
February 8, 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28169297/comparative-influenza-protein-interactomes-identify-the-role-of-plakophilin-2-in-virus-restriction
#9
Lingyan Wang, Bishi Fu, Wenjun Li, Girish Patil, Lin Liu, Martin E Dorf, Shitao Li
Cellular protein interaction networks are integral to host defence and immune signalling pathways, which are often hijacked by viruses via protein interactions. However, the comparative virus-host protein interaction networks and how these networks control host immunity and viral infection remain to be elucidated. Here, we mapped protein interactomes between human host and several influenza A viruses (IAV). Comparative analyses of the interactomes identified common and unique interaction patterns regulating innate immunity and viral infection...
February 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28159667/a-novel-method-for-detection-of-h9n2-influenza-viruses-by-an-aptamer-real-time-pcr
#10
Issam Hmila, Manoosak Wongphatcharachai, Nacira Laamiri, Rim Aouini, Boutheina Marnissi, Marwa Arbi, Srinand Sreevatsan, Abdeljelil Ghram
H9N2 Influenza subtype has emerged in Tunisia causing epidemics in poultry and resulting in major economic losses. New mutations in their hemagglutinin and neuraminidase proteins were acquired, suggesting their potential to directly infect humans. Effective surveillance tools should be implemented to help prevent potential spillover of the virus across species. We have developed a highly sensitive real time immuno-polymerase chain reaction (RT-I-PCR) method for detecting H9N2 virus. The assay applies aptamers as ligands to capture and detect the virus...
January 31, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28159160/other-community-respiratory-viruses
#11
REVIEW
Richard G Wunderink
Polymerase chain reaction-based diagnosis has become the standard for viral pneumonia and other respiratory tract infections. Expansion of respiratory viral panels (RVPs) outside of influenza and, possibly, respiratory syncytial virus has led to the ability to diagnose viral infections for which no approved specific antiviral treatment exists. Careful clinical evaluation of the patient with a positive RVP is, therefore, critical given the limited repertoire of treatments. Generic treatments with intravenous immunoglobulin, ribavirin, and interferons may benefit select severe viral pneumonia patients, whereas cidofovir has activity for severe adenoviral pneumonia...
March 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/28159158/diagnosing-viral-and-atypical-pathogens-in-the-setting-of-community-acquired-pneumonia
#12
REVIEW
Grant W Waterer
The 'atypical' pathogens causing pneumonia have long been problematic for physicians because we have had to rely on serologic tests to make a diagnosis. The introduction of polymerase chain reaction techniques revolutionized the diagnosis of respiratory infections and now a new wave of technologies promising faster, cheaper, and more comprehensive testing are becoming available. This review focuses principally on the diagnosis of Legionella, Mycoplasma, and influenza infections, but also covers recent publications on the cutting edge of diagnostic tools likely to transform the field of infectious diseases over the coming decade...
March 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/28154333/structural-and-biochemical-analyses-on-the-rna-dependent-rna-polymerase-of-influenza-virus-for-development-of-novel-anti-influenza-agents
#13
Dai Hatakeyama
 The PA, PB1, and PB2 subunits, components of the RNA-dependent RNA polymerase of influenza A virus, and the nucleoprotein (NP) interact with the genomic RNA of influenza viruses and form ribonucleoproteins. Especially, the PB2 subunit binds to the host RNA cap [7-methylguanosine triphosphate (m(7)GTP)] and supports the endonuclease activity of PA to "snatch" the cap from host pre-mRNAs. In this study, we describe a novel Val/Arg/Gly (VRG) site in the PB2 cap-binding domain, which is necessary for interaction with acetyl-CoA found in eukaryotic histone acetyltransferases (HATs)...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28146320/influenza-antivirals-currently-in-late-phase-clinical-trial
#14
Paulina Koszalka, Danielle Tilmanis, Aeron C Hurt
Influenza antiviral drugs are important for the control of influenza, most specifically for the treatment of influenza patients with severe disease following infection with a seasonal influenza virus, a newly emerging influenza strain, or in the event of a pandemic. Many influenza antivirals that are currently under investigation in late stage clinical trials differ in their mechanism of action compared to drugs currently licensed for the treatment of influenza. Nitazoxanide and DAS181 target components of the host cell and alter the ability of the virus to replicate efficiently, while small molecule drugs such as T705, JNJ63623872 and S-033188 bind to the viral polymerase complex and restrict viral replication...
February 1, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28144057/respiratory-viruses-in-acute-exacerbations-of-chronic-obstructive-pulmonary-disease
#15
Parvaiz A Koul, Hyder Mir, Shabir Akram, Varsha Potdar, Mandeep S Chadha
OBJECTIVE: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) cause significant morbidity, mortality, and an inexorable decline of lung function. Data from developed countries have shown viruses to be important causes of AECOPD, but data from developing countries like India are scant. We set out to determine the contribution of viruses in the causation of hospitalized patients with AECOPD. METHODS: Twin nasopharyngeal/oropharyngeal swabs collected from 233 patients admitted with an acute AECOPD and tested for respiratory viruses including respiratory syncytial virus A and B, parainfluenza were (PIV) 1, 2, 3, and 4, human metapneumovirus (hMPV) A and B, influenza A and B, enterovirus, corona NL65, OC43, and 229E viruses, adenovirus 2 and 4, rhinovirus, and bocavirus, by duplex real time reverse-transcription polymerase chain reaction (qRT-PCR) using CDC approved primers and probes...
January 2017: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/28139390/persistence-of-influenza-on-surfaces
#16
K-A Thompson, A M Bennett
BACKGROUND: Close contact transmission (either direct or large droplet/droplet nuclei) is considered the main driver of influenza outbreaks but there is limited information regarding the role of fomites in transmission. AIM: To investigate the surface stability of influenza strains and thereby the role of fomites in transmission. METHODS: The viability and quantitative reverse transcription-polymerase chain reaction (qt-RT-PCR) signal of five influenza strains (A/PR/8/34/H1N1, A/Cal/7/09/H1N1, A/Cal/4/09/H1N1, A/Sol/54/06/H1N1, and A/Bris/59/07/H1N1) seeded on to three surfaces (cotton, microfibre, and stainless steel) were assessed over time...
February 2017: Journal of Hospital Infection
https://www.readbyqxmd.com/read/28127953/detection-of-influenza-virus-subtype-a-by-polymerase-chain-reaction-who-external-quality-assessment-programme-summary-analysis-2016
#17
(no author information available yet)
No abstract text is available yet for this article.
27, 2017: Relevé épidémiologique Hebdomadaire
https://www.readbyqxmd.com/read/28126917/an-in-vitro-fluorescence-based-study-of-initiation-of-rna-synthesis-by-influenza-b-polymerase
#18
Stefan Reich, Delphine Guilligay, Stephen Cusack
Influenza polymerase replicates, via a complementary RNA intermediate (cRNA), and transcribes the eight viral RNA (vRNA) genome segments. To initiate RNA synthesis it is bound to the conserved 5' and 3' extremities of the vRNA or cRNA (the 'promoter'). 5'-3' base-pairing in the distal promoter region is essential to position the template RNA at the polymerase active site, as shown by a new crystal structure with the 3' end threading through the template entry tunnel. We develop fluorescence polarization assays to quantify initiation of cap-primed (transcription) or unprimed (replication) RNA synthesis by recombinant influenza B polymerase bound to the vRNA or cRNA promoter...
January 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28124966/-a-case-of-bronchiolitis-obliterans-secondary-to-human-metapneumovirus-bronchiolitis
#19
Osman Yeşilbaş, Esra Şevketoğlu, Hasan Serdar Kıhtır, Mey Talip Petmezci, Elif Bato, Seda Balkaya, Nevin Hatipoğlu, Mert Ahmet Kuşkucu, Figen Palabıyık, Erkan Çakır
Human metapneumovirus (hMPV), formerly classified in Paramyxoviridae family is now moved into Pneumoviridae, which was described as a novel family. It causes upper and lower respiratory tract infections (LRTIs) usually in children younger than five years old. The recent epidemiological studies indicated that hMPV is the second most frequently detected virus in LRTIs of young children, following the respiratory syncytial virus (RSV). Bronchiolitis obliterans (BO) is a chronic obstructive lung disease characterized by fibrosis of the distal respiratory airways...
October 2016: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28124644/differences-in-innate-immune-response-gene-regulation-in-the-middle-ear-of-children-who-are-otitis-prone-and-in-those-not-otitis-prone
#20
Ravinder Kaur, Janet Casey, Michael Pichichero
OBJECTIVE: Acute otitis media (AOM) causes an inflammatory response in the middle ear. We assessed differences in innate immune responses involved in bacterial defense at onset of AOM in children who were stringently defined as otitis prone (sOP) and children not otitis prone (NOP). STUDY DESIGN: Innate immune genes analysis from middle ear fluid (MEF) samples of children. METHODS: Genes of toll-like receptors (TLR), nod-like and retinoic acid-inducible gene-I-like receptors, downstream effectors important for inflammation and apoptosis, including cytokines and chemokines, were studied from MEF samples by using a real-time polymerase chain reaction array...
November 1, 2016: American Journal of Rhinology & Allergy
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